An experimental breast cancer vaccine has been shown to safely generate a strong immune response against a key tumor protein in a small study of over 70 women with metastatic breast cancer. The results, published in the journal «JAMA Oncology“, show it 80% of the women treated were still alive ten years after receiving the vaccinefive years longer than with existing therapies.
However, “as this is not a randomized clinical trial, the results should be considered preliminary, but they are promising enough that the vaccine is now being evaluated in a larger randomized clinical trial,” says lead author Mary L. Disis. , of the University of Washington School of Medicine in Seattle (EEUU.).
Breast cancer is, in general, a tumor with a good prognosis, but some subtypes are more aggressive. One of the variants with the highest mortality rate is HER2 positive, as altering this gene causes signals to be passed on to cancer cells so that they grow faster than normal, accelerating the progression of the disease. This implies a greater risk of metastasis and the spread of cancer to other different organs.
The Phase I study was designed to evaluate the safety of a vaccine that targets a protein called human epidermal growth factor receptor 2 (HER2) and to see if it generated an immune response to the protein.
HER2 is found on the surface of many cells, but up to 30% of breast cancers are known to be produced up to 100 times more HER2 than normal cells. These HER2-positive tumors tend to be more aggressive and are more likely to recur after treatment, but the overproduction of HER2 also triggers an immune reaction that can be beneficial.
Up to a hundred times more HER2 is produced in 30% of breast cancers than in normal cells
In particular, patients with HER2-positive breast cancer who develop a type of immune response called cytotoxic (or cell-killing) immunity are less likely to reappear after treatment and have a longer overall survival than those who do not. . .
To stimulate this type of response, the researchers made a DNA vaccine.
Unlike protein vaccines, which typically contain a protein or part of a protein that you want the immune system to target, DNA vaccines contain DNA instructions for the target protein.
Once injected, this DNA is absorbed by the cells at the injection site, which begin producing the protein encoded in the vaccine’s DNA instructions. The cells will then present the protein to the immune system, a process that is likely to generate a strong cytotoxic immune response.
The vaccine used in this study contained DNA instructions for a portion of HER2 that is usually found inside the cell.. This intracellular portion is known to elicit stronger cytotoxic immune responses.
In all, 76 women who had metastatic cancer were enrolled in the study. All of them had either completed a standard course of therapy and achieved complete remission or had only one tumor left in the bone, which tends to grow slowly.
Study participants were divided into three groups, with each participant receiving three injections: one group received three low-dose injections (10 mcg); another an intermediate dose of 100 mcg and the third 3 high dose injections, 500 mcg.
They also received the granulocyte-macrophage colony-stimulating factor (GM-CSF) immunostimulating drug, which promotes cytotoxic immunity.
The team followed the participants for 3-13 years (the mean follow-up was nearly 10 years). Long-term follow-up is important because HER2 is found on many other cell types. The researchers wanted to make sure that vaccination did not trigger an autoimmune response against other healthy tissues that carry HER2 over time..
“The results showed that the vaccine was very safe,” Disis says. In fact, the most common side effects seen in about half of the patients were very similar to those seen with Covid vaccines: redness and swelling at the injection site and possibly some fever, chills, and flu-like symptoms.
Participants did much better than would be expected in patients with similar stages of breast cancer
The vaccine also successfully stimulated the desired cytotoxic immune response without triggering severe side effects. and the strongest immune response appeared in patients who received the average dose.
Although the study wasn’t designed to see if the vaccine could slow or prevent cancer progression, the participants fared much better than would be expected in patients with similar stages of breast cancer, about half of whom would die within 5. years from treatment.
“We have been following these women for ten years and 80% of them are still alive”, Disis points out, adding that if the results of the new phase II randomized controlled trial of the vaccine are positive, it will be a strong signal to start a definitive study. phase III. “I have high hopes that we are close to a vaccine that can effectively treat breast cancer patients.”
